DESCRIPTION: (Modified from application). Gene therapy may replace chronic constant intravenous catheter and continuous infusion, or the alternative lung transplantation, for the treatment of the otherwise fatal disease of primary pulmonary hypertension. It is proposed that transfection of the lungs with the prostaglandin synthase (PGHS) gene will decrease pulmonary vascular reactivity by increasing generation of prostacyclin and PGE2. Transfection of the pulmonary vascular endothelium by intravenous administration of a transgene as a plasmid cationic lipid complex has previously been demonstrated by these investigators. Phase I of the proposed study will determine whether pulmonary vascular reactivity can be decreased by in vivo PGHS gene transfer through either intravenous or intra-airway routes in normal animals. Phase II studies will be conducted in animal models of pulmonary hypertension. Studies of primary pulmonary hypertension are considered preliminary safety and efficacy studies for the much larger group of patients with secondary pulmonary hypertension and cor pulmonae. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE